The program described above proposes to elucidate the metabolism and mechanism of action, including the question of organospecificity, of the powerful, chemically related colon carcinogens 1,2-dimethylhydrazine, azoxymethane and methylazoxymethanol acetate. During this research, various genetic differences in susceptibility to chemical carcinogenesis will be examined with respect to carcinogen metabolism. Enzme inducers and inhibitors, especially those known to be present in the environment, will also be used in these studies no only as useful tools for clarifying the biochemical reactions involved, but also for the purpose of providing analogies which may be of potential importance in the human condition. In addition, the program proposes to investigate the possibility of the endogenous formation of the colon carcinogen, azoxymethane, from methylamine, a ubiquitous metabolic intermediate.